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YAP-mediated glycolysis promotes pulmonary arterial smooth muscle cell proliferation in pulmonary arterial hypertension
Failure‐Mechanism‐Driven Inverse Design and Optimization Procedure for Battery Lifetime Extension
Abstract Precise design and optimization of lithium‐ion batteries (LIBs) remain challenging due to their intricate, dynamic degradation mechanisms and the competitive interactions. Building upon a mechanism‐driven LIB lifetime prediction model based on capacity degradation, we propose an inverse design and optimization procedure (IDOP) that integrates parameter sensitivity analysis (PSA) and multiobjective optimization (MOO). For modeling, we employ directly adjustable design parameters of the anode and electrolyte and indirectly derived interfacial characteristics of anode/electrolyte interface. The PSA results indicate that areal density, particle radius, and interface characteristics exert a significant influence on battery lifetime. Using data from a reference LiNi 0.6 Co 0.1 Mn 0.3 O 2 ||graphite pouch cell for assessment, the MOO predicts a battery lifetime extension of up to 26.63% (70.97%) and 32.76% (138.41%) at 25 and 45 °C by optimizing direct (indirect) factors, respectively. Evaluation of the MOO‐optimized factors using the failure‐mechanism‐driven model demonstrates remarkable alignment in capacity degradation trajectories. The IDOP framework is a promising approach to improve the design and optimization efficiency for developing better LIBs.
Retraction: Exploring the impact of renewable energy on economic growth and carbon emissions: Evidence from partial least squares structural equation modeling
The DID of CAPS-1 anchors plasma membrane to promote vesicle exocytosis
Potential phosphorylation of Liprin-α1 at threonine 701 regulates integrin-mediated cell motility
A dynamic protein network at the leading edge of motile cells is needed to coordinate events required for efficient cell motility. Previous work has shown that the Ser/Thr kinase DYRK3 affects the assembly of this network, and phosphorylates its component Liprin-α1, a scaffold protein regulating adhesion turnover and cell motility. We have looked for phospho-sites of Liprin-α1 relevant for the regulation of cell motility, by examining the role played by serine/threonine residues phosphorylated within the intrinsically disordered regions of Liprin-α1. Phospho-null mutations within either the amino-terminal or the carboxy-terminal disordered regions affect Liprin-α1 phosphorylation induced by DYRK3. Functional analysis shows that mutations within the amino-terminal region do not affect cell motility, while a set of carboxy-terminal mutations reduces the positive effects of Liprin-α1 on cell spreading on the extracellular matrix. Among several candidate phospho-sites in this protein region, we identify Thr 701 as one of the potential main targets of DYRK3 activity in Liprin-α1. The phospho-null mutation of Thr 701 specifically inhibits Liprin-α1–induced potentiation of cell spreading on fibronectin. Our findings contribute to highlight the complexity of the regulation of Liprin-αprotein functions by phosphorylation/dephosphorylation events. Given the involvement of Liprin-α proteins in tumor cell motility and invasion, in-depth understanding of this regulatory complexity may highlight new possibilities for therapeutic intervention.
Pathogenic variants in KCTD1 disrupt cAMP signaling and cellular communication associated with developmental pathways
Superhydrophilic Fe <sup>IV</sup> <sub>2</sub> Mn <sup>II</sup> Nanocluster: A Combined Diagnostic and Therapeutic Agent
Abstract We report here an atomically precise nanocluster, (NH 4 ) 2 Mn II (H 2 O) 2 [Fe IV (L)] 2 ·11H 2 O ( Fe 2 Mn ). This system was designed to harness superhydrophilic interactions to enhance magnetic resonance imaging (MRI), while permitting photoacoustic imaging (PAI) and photothermal antitumor therapy. It was synthesized using Fe‐HDCL, an Fe(IV) system with strong near infrared (NIR) photothermal conversion capabilities, as a precursor and manganese(II) ion that allows for MRI as the metal center. Fe 2 Mn not only produces a useful photothermal effect but also provides for MRI enhancement with a longitudinal relaxivity ( r 1 ) of 7.67 mM −1 s −1 at 0.5 T and 6.02 mM −1 s −1 at 3.0 T, values that are nearly double those of common gadolinium‐based contrast agents (e.g., Gd‐DTPA, r 1 ≈ 3.0 ∼ 4.0 mM −1 s −1 ). This enhanced relaxivity arises from two para ‐positioned water coordination sites ( q = 2) on the manganese(II) ion and robust hydrogen bonding between hydrophilic groups on the Fe‐HDCL surface and surrounding water molecules, forming a second‐sphere hydration shell. As detailed below, the nanocluster of this study ( Fe 2 Mn ) enables high‐quality dual‐mode MR/PA imaging and effective low‐dose (25 µmol·kg −1 ) laser‐triggered photothermal tumor ablation. The present study thus demonstrates how rationally designed superhydrophilic architectures that control both inner sphere coordination and second sphere hydration dynamics can give rise to more effective theranostic agents.
Correction: Genomic and bioacoustic variation in a midwife toad hybrid zone: A role for reinforcement?
Auxin-induced depletion of human CCR4-NOT subunits reveals opposing functions of CNOT1 and CNOT4 in mRNA metabolism
Identification of key genes associated with idiopathic pulmonary fibrosis and sarcopenia by bioinformatics analysis
Background Idiopathic pulmonary fibrosis (IPF) and sarcopenia significantly affect patients’ quality of life. The progression and worsening of these conditions are often associated with endoplasmic reticulum (ER) stress, a key cellular stress–response mechanism. This study aimed to investigate the involvement of ER stress in cellular dysfunction in IPF and sarcopenia by identifying ER stress-related crosstalk genes (ERSRCGs). Methods Differential gene expression and weighted gene co-expression network analysis (WGCNA) were used to identify ERSRCGs. Functional enrichment analyses, including the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis (GSEA), were performed to categorize associated pathways. Least absolute shrinkage and selection operator (LASSO) regression was applied to construct diagnostic models for sarcopenia and IPF. The CIBERSORT method was used to examine immune infiltration, and GeneMANIA was used to construct the protein–protein interaction (PPI) network. Results A total of 13 ERSRCGs were substantially associated with sarcopenia and IPF. GO and KEGG analyses revealed enrichment in amino acid metabolism and xenobiotic metabolism pathways. GSEA and GSVA further highlighted the involvement of these genes in multiple biological processes and signaling pathways. LASSO regression identified CTH and IDI1 for IPF, and FOXO1 , CTH, HSD11B1, GSTK1 , and SPTSSA for sarcopenia. Immune infiltration analysis revealed significant correlations between ERSRCGs and immune cell populations in both diseases. Conclusion This study provides novel insights into the interrelated molecular pathways between sarcopenia and IPF, underscoring the potential of ERSRCGs as diagnostic biomarkers and therapeutic targets. The developed diagnostic models highlight key genes that could significantly improve the early detection and risk assessment strategies for these conditions.
SH2-mediated steric occlusion of the C2 domain regulates autoinhibition of SHIP1 inositol 5-phosphatase
Comprehensive bulk and single-cell RNA sequencing uncovers senescence-associated biomarkers in therapeutic mesenchymal stem cells
Post-quantum-inspired scalable blockchain architecture for internet hospital systems with lightweight privacy-preserving access control
The increasing adoption of Internet hospital systems—enabled by the real-time data streaming capabilities of the Internet of Medical Things (IoMT)—has intensified the need for secure, scalable, and low-latency data management infrastructures. Existing blockchain-based solutions often fail to meet these requirements, particularly under high-frequency workloads and stringent privacy demands. To address these limitations, this study proposes a simulation-based post-quantum-inspired alliance blockchain architecture tailored for Internet hospital systems. The framework incorporates four key innovations: (1) a Kyber-inspired hybrid encryption simulation, reducing encryption and decryption times by 72.3% and 74.4%, respectively, compared to RSA-2048; (2) a lightweight patient-centric access control mechanism based on authorization proofs achieving an average verification latency of ∼0.002 ms; (3) a Raft-based scalable consensus protocol, tested under a synchronous constant-delay network assumption, reducing consensus latency by 92.3% while supporting up to 1000 nodes with sub-150 ms finality; and (4) a fault-tolerant IoMT data ingestion layer using 3-of-5 median filtering, sustaining 90–96.2% sensor correction accuracy under varying fault injection rates. The system is prototyped in Google Colab Pro using synthetic data from 1000 virtual patients. Comparative benchmarks against PBFT and RSA-based systems show a fivefold increase in throughput, ∼9.4–12.3% energy savings per transaction, and ∼14% lower memory consumption during encryption. With a modest daily storage footprint (∼15 MB/day), the proposed solution is both resource-efficient and deployment-ready in simulation environments. These results confirm the potential of this architecture to enable trustworthy, energy-aware, and real-time blockchain infrastructures for next-generation digital healthcare ecosystems.
Prolintane analogs as hybrid monoamine transporter ligands: Structural determinants and species differences
Antineoplastic effect of anastrozole-loaded polymer nanocapsules on malignant human breast cancer cells (MCF-7)
Expression of concern: Enhancement of auranofin-induced apoptosis in MCF-7 human breast cells by selenocystine, a synergistic inhibitor of thioredoxin reductase
Endocannabinoid oxygenation by prostaglandin H synthase-2: Chemistry and biology
Sex inference based on convolutional neural network analysis of fingerprint data
High‐Throughput Synthesis and Screening of a Cyanimide Library Identifies Selective Inhibitors of ISG15‐Specific Protease mUSP18
Abstract High‐throughput screening (HTS) of large compound collections is a critical early step in many drug discovery programs. Its success depends heavily on the quality of the compound libraries used, and as such, the development of targeted libraries has emerged to enhance the effectiveness of HTS efforts. However, the acquisition of such libraries remains costly and labor‐intensive, often yielding compound quantities far exceeding required amounts. We present a high‐throughput synthesis‐to‐screening method for the efficient in‐plate generation and immediate HTS of a deubiquitinase (DUB)‐focused compound library. Central to our approach is the Echo acoustic liquid handler, which transfers nanoliter volumes of DMSO‐based solutions, facilitating miniaturized synthesis directly in 1536‐well plates. We constructed a library of 7536 compounds featuring a DUB‐privileged cyanimide warhead and screened against twelve ubiquitin(‐like) proteases. This identified two structurally related molecules with selective inhibitory activity against the interferon‐stimulated gene 15 (ISG15) protease mUSP18, which we further developed into a first‐in‐class mUSP18 inhibitor with 35 nM potency. This compound, BB07CA902, demonstrated exceptional specificity for mUSP18 across 41 DUBs and effectively increased ISGylation levels in cells by inhibiting mUSP18 activity. Our technology enables the efficient preparation of large DUB‐targeted cyanimide‐based libraries, which will accelerate future DUB inhibitor development.
Innovative design and evaluation of medical nebulizer for preschool children: A user demand-driven approach
Aims To enhance the user experience and satisfaction of children’s medical nebulizers, and to improve adherence and the efficacy of nebulization treatments for children, this study explores an innovative design and evaluation method for children’s medical nebulizers from the perspective of user needs. Methods Firstly, this study conducts a thorough analysis of user behaviors and their potential needs for children’s medical nebulizers through field observations, User Journey Mapping (UJM), relevant user interviews, and the KJ method, thereby constructing a hierarchical model of demand indicators. Next, the Analytic Hierarchy Process (AHP) is employed to calculate the weight and priority ranking of each indicator, effectively identifying the crucial demand indicators that influence nebulizer design. Based on the findings from the demand analysis, an innovative design practice for children’s medical nebulizers is carried out. Finally, the fuzzy comprehensive evaluation (FCE) method is used to assess the user satisfaction of the proposed design scheme and an existing nebulizer product case used in children’s hospitals and compare the results to verify the feasibility and effectiveness of the design approach and scheme in this study. Conclusion The results indicate that the combined application of UJM, the KJ method, AHP, and FCE can help designers more accurately capture diverse user needs, enhance the scientific rigor and rationality of design and evaluation processes for children’s medical nebulizers, and ultimately produce products with higher user satisfaction. This study contributes to the field by providing a systematic framework for the design and evaluation of preschool-aged children’s medical nebulizers, offering theoretical guidance and practical reference for future designers.